C-X-C chemokine receptor 2 correlates with unfavorable prognosis and facilitates malignant cell activities via activating JAK2/STAT3 pathway in non-small cell lung cancer

This study aimed to investigate the correlation of C-X-C chemokine receptor 2 (CXCR2) with clinicopathological characteristics and survival in non-small cell lung cancer (NSCLC) patients and further explore its effect on proliferation, apoptosis, invasion, stemness, chemosensitivity as well as JAK2/STAT3 pathway in NSCLC cells. The expression of CXCR2 in tumor tissues and adjacent tissues from 340 NSCLC patients received surgery was detected by immunohistochemistry. CXCR2 overexpression and knockdown were constructed through plasmid transfection and the effect of CXCR2 dysregulation on cell proliferation, apoptosis, invasion, stemness, chemosensitivity as well as its regulatory effect on JAK2/STAT signaling pathway was assessed in NCI-H1437 cells and NCI-H1299 cells. CXCR2 expression was higher in tumor tissues than that in paired adjacent tissues, and it was correlated with poor pathological differentiation, greater tumor size, lymph node metastasis, higher TNM stage and poor survival in NSCLC patients. In vitro, CXCR2 expression was increased in human NSCLC cell lines compared with human normal lung bronchus epithelial cells. CXCR2 promoted cell proliferation and invasion, while suppressed cell apoptosis in NCI-H1437/NCI-H1299 cells. Additionally, CXCR2 increased CD133⁺ cell rate and cell sphere-forming ability, while reduced chemosensitivity to cisplatin and gemcitabine in NCI-H1437/NCI-H1299 cells. Besides, CXCR2 activated the JAK2/STAT3 signaling pathway in NCI-H1437/NCI-H1299 cells. In conclusion, the clinical implication and the molecular function of CXCR2 discovered in our study reveal the potential of CXCR2 as a future target for disease monitoring and treatment of NSCLC.